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Epistatic buffering of fitness loss in yeast double deletion strains

Abstract

Interactions between deleterious mutations have been insufficiently studied1,2, despite the fact that their strength and direction are critical for understanding the evolution of genetic recombination3,4 and the buildup of mutational load in populations5,6. We compiled a list of 758 yeast gene deletions causing growth defects (from the Munich Information Center for Protein Sequences database and ref. 7). Using BY4741 and BY4742 single-deletion strains, we carried out 639 random crosses and assayed growth curves of the resulting progeny. We show that the maximum growth rate averaged over strains lacking deletions and those with double deletions is higher than that of strains with single deletions, indicating a positive epistatic effect. This tendency is shared by genes belonging to a variety of functional classes. Based on our data and former theoretical work8,9,10, we suggest that epistasis is likely to diminish the negative effects of mutations when the ability to produce biomass at high rates contributes significantly to fitness.

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Figure 1: Functional classification according to the 'biological process' annotations in the yeast Gene Ontology slim (see URL in Methods).
Figure 2: Growth effects of single and double gene deletions.
Figure 3: Frequency distribution of the epistatic effect ε.
Figure 4: Functional analysis of genetic interactions.
Figure 5: Positive epistasis in simple metabolic networks.

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Acknowledgements

We thank B. Korzeniewski, P. Koteja and S.P. Otto for advice and comments. This work was supported by a grant from the State Committee for Scientific Research of Poland.

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Authors

Contributions

L.J. performed the experiments and data analyses. R.K. wrote the paper. Both authors planned research and discussed results.

Corresponding author

Correspondence to Ryszard Korona.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Precision and repeatability of growth rate estimates. (PDF 187 kb)

Supplementary Fig. 2

Repeatability of extreme estimates. (PDF 94 kb)

Supplementary Table 1

List of strains and crosses. (PDF 521 kb)

Supplementary Table 2

Results of GLM for the first round of crosses. (PDF 4 kb)

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Jasnos, L., Korona, R. Epistatic buffering of fitness loss in yeast double deletion strains. Nat Genet 39, 550–554 (2007). https://doi.org/10.1038/ng1986

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